%0 Journal Article
%T Nelotanserin, a selective 5-HT2A receptor inverse agonist, attenuates aspects of nicotine withdrawal but not reward in mice.
%A Buzzi B
%A AlSharari SD
%A Walentiny DM
%A Damaj MI
%J Behav Brain Res
%V 467
%N 0
%D 2024 Jun 5
%M 38677331
%F 3.352
%R 10.1016/j.bbr.2024.115019
%X Nicotine smoking contributes to many preventable disabilities, diseases and deaths. Targeting nicotine reward and withdrawal is a basis for the majority of smoking cessation pharmacotherapies. Due to the emergence of interest in 5-HT2A receptor modulators for numerous psychiatric disorders, we investigated the effect of nelotanserin, a 5-HT2A receptor inverse agonist, on nicotine reward and withdrawal in ICR mice. In nicotine-dependent mice, nelotanserin dose-dependently reduced somatic signs of nicotine withdrawal and thermal hyperalgesia as measured in the hot plate test. However, nelotanserin had no effect on anxiety-like behavior and failed to reduce nicotine reward as measured in the conditioned place preference test. Our results suggest that inverse agonism of the 5-HT2A receptor may be a feasible novel mechanism for smoking cessation by reducing both physical withdrawal and thermal hyperalgesia associated with nicotine abstinence but may require complementary pharmacotherapies targeting affective and reward-associated decrements to improve cessation outcomes.